Various stereoselective strategies have been devised for the synthesis of 2-amino alcohols, relying on: intramolecular opening of epoxides (Roush et al., J. Org. Chem., 50, 3752 (1985)); intramolecular Michael reactions (Hirama et al., J. Amer. Chem. Soc., 107, 1797 (1985); reduction of a-aminoketones (Fujita et al., J. Amer. Chem. Soc., 106, 4629 (1984)); allylic sulfoxide 2,3-sigmatropic rearrangements of Diels-Alder adducts (Garig et al., J. Amer. Chem. Soc., 106, 7861 (1984)); nitro-aldol reactions (Hanessian et al., Tetrahedron Letters, 26, 1261 (1985)); organometallic additions to a-alkoxyimines (Mukaiyama et al., Chem. Lett., 671 (1985)); or organometallic additions to sulfinimines (Fuganiti et al., J. Org. Chem., 48, 910 (1983) and Fronza et al., J. Carbohydrate Chem., 2, 1225 (1983)).
The last strategies discussed above, i.e. organometallic additions, although attractive, are not entirely satisfactory inasmuch as isolation of imines is often problematic, and preparation of sulfinimines requires strongly basic conditions which may epimerize substrates.
Hydrazone derivatives of aldehydes and ketones have been used extensively as substrates for enolate derived chemistry affording chiral alkylation products quite resistant to racemization. However, only limited or preliminary reports of their electrophilic reactions with organometallic reagents have appeared (Takohashi et al., J. Chem. Soc, Chem. Comm., 668 (1979) and Marxer et al., Helv. Chim. Acta, 47, 1101 (1964).
Surprisingly, we have found that 1,1-dimethylhydrazones provide high threo diastereoselectivity on reaction with organo lithium reagents and eliminate the problems associated with imine derivatives. The approach provides an attractive route to threo 2-amino alcohols after hydrogenolytic cleavage of the intermediate hydrazines.